Small Molecule · ITI-214

Lenrispodun (ITI-214)

Phase 2Intra-Cellular Therapies, Inc. (ITCI)

Potent, selective, orally bioavailable, CNS-penetrant phosphodiesterase 1 (PDE1) inhibitor originated by Intra-Cellular Therapies (now part of Johnson & Johnson). In clinical development for the motor and non-motor symptoms of Parkinson's disease as an adjunct to levodopa; also studied in heart failure and cognition. Mechanistically raises intracellular cyclic nucleotides (cAMP/cGMP) in dopaminoceptive neurons, potentiating dopamine-replacement signaling.

Also known as: ITI-214, IC-200214, Lenrispodun, 1160521-50-5

Data current as of

Modality
Small molecule
Chemical class
pyrazolopyrimidinone, fluoropyridine
Chemistry
Single enantiomer
Mechanism
PDE1B inhibitor
Highest phase
Phase 2
Lead indication
Parkinson's disease
Developer
Intra-Cellular Therapies, Inc. (ITCI)
Trials
2 tracked · 37 sites
Next catalyst
2025 — Topline data (Parkinson's disease)

Mechanism of action

Lenrispodun (ITI-214) is a potent and highly selective inhibitor of phosphodiesterase 1 (PDE1), a Ca2+/calmodulin-dependent dual-specificity phosphodiesterase that hydrolyzes cAMP and cGMP. It inhibits all three human PDE1 isoforms (PDE1A, PDE1B, PDE1C) at picomolar Ki (overall Ki ~58 pM; PDE1A 34 pM, PDE1B 380 pM, PDE1C 37 pM per Snyder et al. 2016), with >1000-fold selectivity over the next-nearest PDE (PDE4D, Ki ~33 nM) and 10,000-300,000-fold over other PDE families. In the CNS, PDE1B is enriched in striatal dopaminoceptive neurons; PDE1 inhibition elevates cyclic-nucleotide signaling downstream of D1 receptors, the proposed basis for potentiating levodopa/dopamine-replacement therapy in Parkinson's disease.

TargetActionAffinity
PDE1BprimaryPDE1BInhibitorKi 380 pMⓘ
PDE1APDE1AInhibitorKi 34 pMⓘ
PDE1CPDE1CInhibitorKi 37 pMⓘ

Formulations

FormulationRouteRegimenPharmacokinetics
Lenrispodun oral (once-daily)
Once-daily oral dosing evaluated across 1, 3, 10, 30 and 90 mg (7-day multiple-ascending-dose Phase 1); Phase 2 Parkinson's disease fixed-dose parallel-group study.
OralOnce daily—
Lenrispodun oral (single-dose)
Single oral doses (liquid solution) of 1.0 and 10.0 mg in the Phase 1 pharmaco-fMRI study in healthy volunteers; acute single oral doses of 30 or 90 mg in the human systolic heart-failure hemodynamic study.
OralSingle dose—

Development timeline

Phase 2Mar 2023 – Dec 2025
  1. UpcomingPhase 2 ITI-214-202 topline in Parkinson's disease (lenrispodun 30 mg vs placebo, Hauser-diary primary at Day 29).
  2. Phase 2 ITI-214-202 reached final completion (primary completion 2025-10-28); 79 patients enrolled. Registry status COMPLETED as of last update 2026-05-22. No topline results disclosed yet.
  3. Phase 2 ITI-214-202 (NCT05766813), lenrispodun 30 mg QD adjunct to levodopa for motor fluctuations in PD, started enrollment.
Phase 1/2Sept 2018
  1. Phase 1/2 multiple-ascending-dose study (NCT03257046, 40 patients, idiopathic PD) completed; reported safe/well-tolerated with exploratory motor/dyskinesia improvement signals at 2018 ANA Annual Meeting.

Lenrispodun (ITI-214) for Parkinson's disease

Phase 2ActiveParkinson's disease indication →

Lenrispodun is in Phase 2 development for Parkinson's disease as an adjunct to levodopa, targeting both motor fluctuations (wearing-off/OFF time, dyskinesia) and non-motor symptoms. The Phase 2 ITI-214-202 study (NCT05766813), a randomized, double-blind, placebo-controlled multicenter trial of 30 mg once-daily vs placebo with a Hauser-diary primary endpoint at Day 29, completed in November 2025 (79 patients enrolled). No topline efficacy results have been publicly disclosed as of 2026-06-25. The program builds on a positive-tolerability Phase 1/2 study (NCT03257046) reported in 2018. Parkinson's disease is the lead CNS indication for the PDE1 program.

Readouts

  • 2025DelayedTopline dataNCT05766813

    Phase 2 ITI-214-202 topline in Parkinson's disease (lenrispodun 30 mg vs placebo, Hauser-diary primary at Day 29).

Clinical trials

NCT05766813ITI-214-202Phase 2Completedn=79

A Randomized, Double-blind, Placebo-controlled Multicenter Study to Assess the Efficacy and Safety of Lenrispodun as Adjunctive Therapy in the Treatment of Patients With Motor Fluctuations Due to Parkinson's Disease

Started Mar 2023· Primary completion Oct 2025· 📍 35 sites across 1 country (United States)

pendingprimaryChange in Hauser Diary-derived motor states (OFF time / ON time / dyskinesia) at Day 29

Lenrispodun 30 mg QD vs placebo, adjunct to levodopa, in PD patients with motor fluctuations (Hoehn & Yahr 2-3 ON). Trial COMPLETED 2025-11-04 (79 enrolled). No topline results posted on CT.gov or announced publicly as of 2026-06-25; outcome captured as pending.

NCT03257046ITI-214-009Phase 1/2Completedn=40

A Randomized, Placebo-Controlled, Double-Blind Study of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of ITI-214 in Patients With Idiopathic Parkinson's Disease

Started Sept 2017· Primary completion Sept 2018· 📍 2 sites across 1 country (United States)

metprimaryTreatment-emergent adverse events over 7 days (safety/tolerability)

Across 1/3/10/30/90 mg once-daily for 7 days (30 active, 10 placebo), ITI-214 was safe and generally well tolerated; most AEs mild, no serious AEs. Exploratory signals of improvement in ON-time without dyskinesia, UPDRS and UDysRS were reported, warranting further study. Presented at 2018 ANA Annual Meeting (poster M217).

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Identifiers

Sources

  1. parkinsonsnewstoday.com — Reference
  2. Intra-Cellular Therapies Presents ITI-214 Phase 1/2 Parkinson's Results at 2018 ANA Annual Meeting — GlobeNewswire / Intra-Cellular Therapies
  3. Lenrispodun as Adjunctive Therapy for Motor Fluctuations Due to Parkinson's Disease (ITI-214-202, NCT05766813) — ClinicalTrials.gov
  4. Preclinical profile of ITI-214, an inhibitor of phosphodiesterase 1, for enhancement of memory performance in rats (Snyder et al., Psychopharmacology 2016) — PDE1A/1B/1C Ki values — Psychopharmacology (PMC)
  5. Safety, Tolerability, PK and PD of Multiple Doses of ITI-214 in Parkinson's Disease (NCT03257046) — ClinicalTrials.gov
  6. Single doses of a highly selective inhibitor of phosphodiesterase 1 (lenrispodun) in healthy volunteers: a randomized pharmaco-fMRI clinical trial — Neuropsychopharmacology / PMC